近日，英国国家心肺研究所教授Clare M. Lloyd及其研究小组报道了气道壁的单细胞空间图揭示了促炎细胞生态系统及其在健康和哮喘中的相互作用。2025年5月21日出版的《自然—免疫学》杂志发表了这项成果。

研究组应用单细胞空间转录组学来揭示健康和哮喘期间气道壁景观。该课题组在健康和哮喘样本中确定了存在于离散空间生态位中的促炎细胞生态系统。这些细胞中心的特点是高水平的趋化因子和报警蛋白表达，以及基质细胞的独特组合。在机制上，该研究组证明了受体，如ACKR1，在局部保留免疫介质，而在这些促炎中枢中表达双调节蛋白的肥大细胞是突出的。尽管进行了抗炎治疗，哮喘气道粘膜在这些细胞生态系统中表现出明显的重塑程序，其特征是关键细胞类型之间的接近度增加。这项研究提供了一个前所未有的气道壁地形视图，揭示了空间壁龛内独特的、特定的生态系统，以作为治疗干预的目标。

据了解，确定组织内细胞的空间位置可以深入了解常驻细胞和炎症细胞之间的相互作用，并且是解耦驱动疾病机制的关键因素。

附：英文原文

Title: A single-cell spatial chart of the airway wall reveals proinflammatory cellular ecosystems and their interactions in health and asthma

Author: Joulia, Rgis, Patti, Sara, Traves, William J., Loewenthal, Lola, Yates, Laura, Walker, Simone A., Puttur, Franz, Al-Sahaf, May, Cahill, Katherine N., Lai, Juying, Siddiqui, Salman, Boyce, Joshua A., Israel, Elliot, Lloyd, Clare M.

Issue&Volume: 2025-05-21

Abstract: Determining spatial location of cells within tissues gives vital insight into the interactions between resident and inflammatory cells and is a critical factor for uncoupling the mechanisms driving disease. Here, we apply single-cell spatial transcriptomics to reveal the airway wall landscape in health and during asthma. We identified proinflammatory cellular ecosystems that exist within discrete spatial niches in healthy and asthma samples. These cellular hubs are characterized by a high level of chemokine and alarmin expression, along with unique combinations of stromal cells. Mechanistically, we demonstrated that receptors, such as ACKR1, retain immune mediators locally, while amphiregulin-expressing mast cells are prominent within these proinflammatory hubs. Despite anti-inflammatory treatments, the asthma airway mucosa exhibited a distinct remodeling program within these cellular ecosystems, marked by increased proximity between key cell types. This study provides an unprecedented view of the topography of the airway wall, revealing distinct, specific ecosystems within spatial niches to target for therapeutic intervention.

DOI: 10.1038/s41590-025-02161-3

Source: https://www.nature.com/articles/s41590-025-02161-3